The goal of this project is to understand the underlying physiological mechanisms of different involuntary movement disorders. The tools we use include clinical neurophysiological methods such as electroencephalography, electromyography, and transcranial magnetic stimulation and neuroimaging with positron emission tomography and functional magnetic resonance imaging. Currently active projects in the Section include studies of tremor, tic and myoclonus. We have completed a study of magnetic resonance spectroscopy in patients with essential tremor that shows a loss of N-acetyl-aspartate in the cerebellum, increasing evidence that the cerebellum is the damaged structure in the disorder. Pursuing the hypothesis whether alcohol has an effect on the central component or the mechanical component in patients with essential tremor, we showed with accelerometry that the improvement in tremor after alcohol ingestion is due to an effect on the central oscillator. We completed studies using clinical neurophysiological testing to identify patients with psychogenic tremor. We showed with accelerometry that psychogenic tremor patients change their tremor frequency while tapping a required frequency, whereas essential tremor and Parkinson tremor patients do not. In addition, psychogenic tremor patients showed higher intraindividual variability while tapping and had difficulties in tapping the required frequency properly. New drugs are needed for treatment of essential tremor. Using tremor accelerometry and clinical tremor testing we showed that 1-Octanol can be safely used and that it significantly reduces tremor amplitude in benign essential tremor in the dose range of 1 mg/kg to 64 mg/kg for up to 6 hours post drug administration. Using voxel-based morphometry, we compared gray matter volume between patients with Tourette's syndrome and matched control subjects. An interim analysis shows reduction of gray matter volume in the prefrontal cortex in Tourette patients. Lafora body disease is a severe, progressive disorder with myoclonus. We completed a treatment trial with a ketogenic diet and showed that patients can benefit from this intervention.